This project involves collection of clinical information and blood samples for genotyping in highly inbred families in Syria from families with many members affected with cleft lip and palate. Cooperation with Syrian local investigators and a month long visit to Syria by Dr. Wyszynski when he was an NIH postdoctoral fellow have resulted in collection of 29 large pedigrees suitable for linkage analysis by the technique of homozygosity mapping. Data collection is ongoing. A 10 cM homozygosity mapping genome scan has been completed with no positive results. A collaboration with Dr. Terri Beaty of JHUSPH has been initiated to increase power. Our samples from the first two large Syrian families were genotyped at CIDR along with Dr. Beaty's samples from several other sites and collaborative linkage analyses have been performed. Fine-mapping of several candidate regions implicated by suggestive lod scores has been performed during the current fiscal year and a paper presenting evidence for linkage to two candidate regions is under preparation. These results suggest possible interaction between two genetic loci that increase risk for non-syndromic oral clefts. The new families are currently being genotyped for candidate regions and these new families will be sent to the Center for Inherited Disease Research for genome wide scan genotyping in the next fiscal year.